Our studies have shown that macrophages are important regulators of erythropoiesis. Regulation may occur at the level of erythropoietin production or by direct effects of macrophages on the growth of pluripotent and committed hematopoietic stem cells. Using a unique model system developed in our laboratory, we have found that macrophage regulation of erythropoiesis is impaired in leukemia. Regulation is restored and the leukemia reversed by replacement therapy with normal macrophages. Our aims are to specifically define the mechanism of macrophage regulation of erythropoiesis, to identify the mediators of this regulation and to determine the defect in leukemia. Our findings will increase our understanding of the control of hematopoiesis and may lead to the development of new, more rational treatments for hematopoietic disorders.